Received for publication Mar 21, 1991; accepted Mar 22, 1991.
PEDIATRICS (ISSN 0031 4005). Copyright © 1991 by the
American Academy of Pediatrics.
SECTION
REPORT
Summary
of
the Annual
Meeting
Section
on Urology,
American
Academy
of
Pediatrics
Barry
A. Kogan, MD
From the Departments of Urology and Pediatrics, University of California, San Francisco, California
Members of the Section on Urology of the Amer-ican Academy of Pediatrics met for 2#{189}days in conjunction with the 59th Annual Meeting of the
American Academy of Pediatrics in Boston,
Mas-sachusetts, October 6 to October 8, 1990. The meet-ing was presided over by Chairperson David T. Mininberg of Cornell University, New York. The papers presented at this meeting that are of interest to the practicing pediatrician are summarized here
according to topic.
The Pediatric Urology Medal, awarded to an individual who has made outstanding contributions to the field of pediatric urology, was presented to
Dr Frank Hinman, Jr. of the University of Califor-nia, San Francisco. Dr Hinman was recognized for
his many years of work dedicated to improving the
urologic care of children. A foremost clinician,
teacher, and researcher, he has contributed partic-ularly to the understanding of urinary tract
infec-tions and bladder dysfunction in children,
particu-larly those children who have “Hinman Syndrome,” the non-neurogenic neurogenic bladder. Dr Hin-man has been a strong advocate for the specialized urologic care of children for many years.
GENITOURINARY NEOPLASMS
Wilms’ tumor is one disease in which there has been impressive progress in recent years, particu-larly with the advent ofeffective chemotherapy that
has enabled these children to have increased
dis-ease-free survival. Montgomery and co-workers from the Mayo Clinic reviewed the experience of patients with bilateral Wilms’ tumor during the past 16 years. Ten-year survival was 69%.
Seventy-five percent of the failures resulted from recurrent disease (which generally occurred early), and 25% resulted from treatment complications. Current recommendations are for initial bilateral renal bi-opsy followed by multimodal treatment, chemo-therapy and radiotherapy, as determined by the tumor stage in the presence or absence of unfavor-able histology. Second- and third-look surgery should proceed thereafter. Several groups addressed the desirability of reducing treatment and thereby treatment complications. Adams and his co-work-ers from Boston Children’s Hospital demonstrated 100% survival (88% disease-free) in 8 patients treated with surgery only for an apparent Stage I Wilms’ tumor. Samowitz and Hanna from New
York University and McLorie and co-authors from The Hospital for Sick Children, Toronto, evaluated the potential of partial nephrectomy for both uni-lateral and bilateral Wilms’ tumor: both found it to be highly effective, although not in accordance with the National Wilms’ Tumor Study Protocol (NWTS). Perhaps the NWTS recommendations
will be reconsidered as more data become available.
BLADDER DYSFUNCTION
The ability to recognize and treat bladder dys-function in children has been one of the major
Hence, there were a large number of research and clinical papers in this section. In the research
por-tion, Rosenthal and co-authors from the Medical
College of Wisconsin found markedly reduced levels
of calcium channel receptors in myelodysplastic
bladders. This may explain partially the mechanism
of bladder dysfunction in these children. Kim and co-workers from the University of California, San
Francisco, investigated the histology of obstructed fetal bladders and demonstrated increased amounts of Type I collagen as well as elastin. Interestingly, the total amount of collagen was not increased,
suggesting that it may not be the amount, but the
type and location, which may account for the blad-der dysfunction. Peters and co-workers from
Bos-ton Children’s Hospital looked at myosin heavy chain composition in obstructed fetal sheep blad-ders and demonstrated that the obstruction
accel-erated the normal developmental shift toward equal
amounts of the two myosin heavy chain iso-forms.
Casale and others from the University of Louisville, as well as Greenfield and Fera from the University of Buffalo, investigated the use of intravesical ox-ybutinin. It seemed to be effective both in animal
preparation as well as in 7 of 9 children with bladder
dysfunction. This method of treatment appears to
have great potential.
Bauer and his co-workers from Boston Children’s Hospital, as well as Kaplan and Richards from
Children’s Memorial Hospital, Chicago, reported follow-up on their techniques of treatment of
chil-dren who have myelodysplasia. Bauer clearly
dem-onstrated the benefits of early prophylactic therapy in newborns with myelodysplasia who are found by
urodynamic studies to be at high risk. There is no
question now that these patients can be identified and that early, aggressive treatment is appropriate. Kaplan reviewed his experience with intravesical bladder stimulation in an effort to rehabilitate blad-der function in children with neurogenic bladder disease. The technique is extremely time- and
la-bor-intensive, and consequently Kaplan tried to predict those patients most likely to respond. He
showed that patients who have neither sensation of
bladder fullness nor detrusor contractions after an
initial trial are unlikely to benefit and should be
offered other therapy. Finally, in a novel study,
Greenfield and Fera from the University of Buffalo
reported urodynamic studies performed before
per-meal surgery in patients with imperforate anus.
Three of the 13 patients had significant bladder
dysfunction. (Interestingly, of these only one had a
significant spinal anomaly.) Eight patients had long-term follow-up and 5 maintained normal
blad-der function.
DIVERSION AND AUGMENTATION
There is general agreement that the selected use of bowel segments in the urinary tract of children with bladder dysfunction has been a major advance.
Riedmiller and associates from Mainz presented
supporting data by demonstrating excellent overall
results over 5 years with use of the “Mainz-Pouch.”
In addition, Leonard and associates from Johns
Hopkins demonstrated a positive experience with
the Benchekroun continent valve for pediatric un-nary reservoirs. In a fascinating and much
dis-cussed presentation, Nasrallah and Aliabadi from
Children’s Hospital in Akron and Gillette
Chil-dren’s Hospital in St. Paul demonstrated that most
reflux in patients with neurogenic bladder dysfunc-tion is secondary to the dysfunction, and antireflux
surgery may not be necessary provided that bladder
augmentation is successful.
Nonetheless, despite these encouraging results, the long-term side effects provoke considerable
con-cern. In fact, Woodhouse and associates from
Lon-don demonstrated delayed linear growth in 45 chil-dren who had continent urinary reservoirs created from bowel. Unfortunately there were no features in particular which would distinguish those who ultimately had impaired growth from the rest.
5ev-eral other groups explored alternatives to reduce
morbidity in these patients. Badiola and co-authors from the University of Minnesota showed that, when the mucosa of the left colon was stripped and the bowel inverted to use the serosal surface as the
urinary lining, a transitional epithelium formed to cover the cystoplasty. However, it was extremely
difficult to strip the epithelium, and bladder calculi
developed in one fourth of the patients. Although promising, this technique is not appropriate for clinical use at this time. In a related study, Klee and associates from Riley Children’s Hospital in
Indianapolis looked at the long-term effects of gas-trocystoplasty as another option to help prevent metabolic abnormalities. In animal experiments, those with gastrocystoplasty survived and in fact
seemed to thrive without electrolyte problems.
However, the animals did develop a number of
histopathologic changes, the cause and potential
carcinogenicity of which remain uncertain. In sum-mary, enterocystoplasty is an extremely useful pro-cedure, but has significant potential side effects. Patients should be selected carefully.
OBSTRUCTION
Treating urinary tract obstruction in children
co-work-ens from Stanford presented data demonstrating that bladder fullness affects renal pelvic pressure and renal pelvic work. Among the important
impli-cations is that bladder fullness must be taken into
consideration when interpreting tests of upper tract
obstruction, especially the diuretic renogram. Buf-fington and co-workers from the University of Cm-cinnati and Peters and co-workers from Boston
Children’s Hospital both presented their data
re-garding the effect of fetal obstruction on pulmonary hypoplasia. Buffington’s work, in a rabbit
prepa-ration, demonstrated a clear relationship.
Interest-ingly, they found no differences from controls in
lung weight, pulmonary compliance, or alveolar septal-wall thickness. Peters’ group, on the other
hand, found significant histologic differences in their obstructive groups as well as improvement, both histologically and functionally, after in utero relief of obstruction. This has important
implica-tions for prenatal treatment.
Several clinical studies evaluated new, refined techniques for diagnosing urinary tract obstruction. Maizels at Children’s Memorial Hospital, Chicago, presented a standardized diuretic renogram termed “The Well-Tempered Renogram.” This technique
involves hydration of the patient before the test, well-defined methods of analysis (including careful
drawing of regions of interest, background
subtrac-tion, and differential function), as well as use of a standardized dose of furosemide (1 mg/kg) and bladder drainage when appropriate. This
refine-ment should help to diminish inteninstitutional
var-iations in the results of renography. Mesrobian and Perry from the University of North Carolina
eval-uated an entirely different technique termed di-uresis pyelography. This method is appropriate
only in patients who have a nephrostomy tube.
Radiolabeled diethylenetriamine pentaacetic acid is
used to fill the system through the tube; after giving
a diuretic, one can evaluate quantitatively the
washout from the completely filled system.
Prelim-mary results of this technique are encouraging. Finally, Palmer and associates at the University of California, Davis, reported preliminary information
on diuretic doppler sonography in neonatal
hydro-nephrosis. Their early results demonstrated that
resistive indices may well be a noninvasive and very
useful method for assessment of urinary obstruc-tion in neonates. Although interesting, all these
techniques require more work.
EXSTROPHY
During the past 25 years, treatment of patients with exstrophy has shifted from diversion to recon-struction. Several papers addressed the issue of
urinary continence in these patients. Weinstein from Detroit Children’s Hospital reported on 18 years of experience. Initial bladder neck
reconstruc-tion was less than successful, but selective use of an artificial sphincter or, more importantly, bladder augmentation achieved satisfactory continence in
80% of patients. Very similar results were obtained
in a larger series reported by Ransley from London. Only 2 of 36 patients had successful continence with bladder neck reconstruction alone; however,
of 80 of 96 patients who ultimately underwent a bladder augmentation procedure, 60 are acceptably dry. Gearhart and Jeffs from Johns Hopkins dis-cussed their experience with patients who had cloa-cal exstrophy. Numerous operations were
per-formed with frequent augmentation and, in many
instances, continent stomas. Innovative and flexi-ble approaches were required in all these patients to find the most suitable solution for each.
ANDROLOGY
The advent of new technologies, eg, flow
cytom-etry and measurement of antisperm antibodies, has
led to a resurgence of interest in testicular
abnor-malities. Skoog and others from Walter Reed Army Medical Center, Washington, DC, as well as Quinn and Brown from Belfast independently described experimental models demonstrating the utility of flow cytometry in the analysis of testicular func-tion. Although their work is preliminary, it does
suggest future benefits. Also working independ-ently, Scherz and others from Children’s Hospital,
San Diego, and Hess and others from New York
Hospital looked at the detection of antisperm
an-tibodies in children. Although Hess found
signifi-cant antisperm antibodies in cryptorchid boys, Scherz failed to find them after testicular biopsy. (Scherz did note a significant variability in the
detection of antibody levels, depending on the
lab-oratory used.) In combined clinical studies, Huff and Hadziselimovic reported several different eval-uations of testicular histology from Children’s
Hos-pital of Philadelphia and Kinderspital, Basel. Their
studies demonstrated evidence of histologic abnor-malities in Leydig cells of cryptorchid testes within the first 7 months of life. In these studies, although the total number of gonocytes was no different in undescended testes and controls, the transforma-tion of gonocytes to Ad spermatogonia was delayed in cryptorchid patients. They also found an
in-creased rate of abnormalities in infants with
incar-cerated hernia. These abnormalities suggest a
chronic, perhaps developmental, problem in
de-scended testis in boys with unilateral monorchia. Histologic findings were normal, implying that the cause of the absent testis was related to torsion and not cryptorchidism. In a highly controversial study,
Koff from Columbus Children’s Hospital
demon-strated that testicular hypertrophy indeed was as-sociated with monorchia. In his report, the size of the contralateral scrotal testis was related inversely to the presence and health of the nonpalpable testis:
eg, the scrotal testis was larger when the
contralat-eral testis was absent than when it was intra-abdominal. Although no exceptions were noted to
the finding in this preliminary report, in the
con-siderable discussion after the paper it was con-cluded that further investigations are needed.
Park-house and Hendry from London reported on
long-term follow-up of a group of men who previously had suffered vasal and epididymal injuries during
childhood orchiopexy or herniorrhaphy. All
pa-tients with unilateral testicular obstruction had
antisperm antibodies, as did 50% of those with
bilateral obstruction. In the former, antibodies
de-creased and sperm count increased in nearly all patients who underwent unilateral orchiectomy of
the obstructed testis. Thus far the pregnancy rate
is 29%. In contrast, very little improvement was seen in patients with bilateral obstruction who underwent reconstructive surgery. Recognition and
treatment of this problem can improve fertility.
They acknowledged, however, that they were study-ing a select group, all of whom exhibited infertility.
The number of men with unilateral testicular
ob-struction who are fertile is uncertain.
OPERATIVE TECHNIQUES
Numerous examples of innovation in pediatric
urology were presented. Thomas and others from
New Orleans reported initial results with rigid
ur-eteroscopy and ureterolithotripsy in children. All
patients were rendered stone-free, but it should be
noted that the group was primarily older. The tech-nique may not be applicable to young children. De
Gennaro from Rome demonstrated the
effective-ness oftrigonoplasty for treatment of vesicoureteral
reflux with a modification of the Gil-Vernet
tech-nique. Farkas from Jerusalem presented excellent results in the treatment of bilateral megaureters
with a modification of an intravesical technique so
that both sides could be easily repaired via a Pfan-nenstiel incision. Hendren and Adams from Boston Children’s Hospital presented their long-term
re-sults in the treatment of 36 patients with the Prune
Belly Syndrome. They demonstrated that by
mdi-vidualizing treatment most patients do well.
How-ever, the syndrome occurs with a spectrum of
se-verity and a number of patients will progress to renal failure despite optimal reconstruction.
Mon-fort from Marseille demonstrated excellent
dos-metic results in abdominal wall reconstruction of patients with the Prune Belly Syndrome. The
um-bilicus is preserved, any intra-abdominal surgery
can be performed through the incision, and the
cosmetic improvement appears to be long-lasting.
Decter from Hershey and Caione from Rome both
demonstrated modifications of commonly per-formed distal hypospadias repairs. Both groups
demonstrated excellent cosmetic results and
mini-mal complications. Leonard and others from Johns
Hopkins demonstrated good results with a
modifi-cation of the Ransley-Cantwell technique for epi-spadias repair. Although this technique appears to
be an improvement over prior concepts, much more work needs to be done in this area. Parrott and Woodard from Atlanta demonstrated excellent re-sults with a modification of Pasarini’s technique
for vaginoplasty in the adrenogenital syndrome. By
adding the transtrigonal approach to lateral labial advancement, they noted excellent cosmetic results
and no significant complications. As others have,
they reported narrowing of the anastomosis when the operation was performed in early childhood.
Bloom from Ann Arbor reported successful scrotal placement of an intra-abdominal testis in 6 of 7
patients with laparoscopic clip ligation of the
sper-matic artery as the first stage of a two-step
orchi-opexy. The seventh patient had undergone previous inguinal surgery and was noted to have a suture that had ligated part of the long vas loop. Although this innovative technique is exciting, questions
re-main about how often it is beneficial to attempt
orchiopexy as opposed to orchiectomy for
intra-abdominal testes.
INFECTION
In a combined session with pediatric nephrology, a number of new investigations into the pathophys-iology and treatment of urinary tract infection were
presented. Lewis and others from the University of Buffalo and Majd and others from National Chil-dren’s Hospital, Washington DC, reported similar experimental studies on renal blood flow changes
associated with vesicoureteral reflux and
expeni-mental acute pyelonephritis. In the absence of
in-fection renal blood flow decreased, primarily with high bladder filling; blood flow changes were mini-mal with reflux. In the presence of infection,
defi-nite focal ischemia was noted, suggesting that this
di-mercaptosuccinic acid (DMSA) scanning reliably predicts those kidneys at risk for pyelonephnitis, and that scarring can also occur with pyelonephritis
unrelated to vesicoureteral reflux, although at a
lesser rate than that seen in patients with reflux. Cam and others from Boston Children’s Hospital measured urinary N-acetylglucosaminidase levels in children with vesicoureteral reflux and reported a direct correlation between N-acetylglucosamini-dase concentration and grade of reflux. Whether
this reflects permanent renal injury or is evidence
of renal damage from sterile reflux remains to be determined. Diamond and others from the Univer-sity of Massachusetts (Worcester) and London studied the natural history of patients with vesico-ureteral reflux and duplicated collecting systems. They noted a spontaneous resolution rate similar
to that for patients with reflux into single systems
and thus felt that a period of observation was justified. Thomas and others from Leeds reported
their experience with the renal damage associated with vesicoureteral reflux when the reflux is
diag-nosed in utero. Significant renal function abnor-malities were discovered in only 17% of those kid-neys exposed to primary reflux but in 86% of those in which sterile reflux was associated with urethral valves or duplex systems. Although their data are
not conclusive, this suggests that many of the renal
abnormalities associated with primary reflux are acquired, in contrast to those seen with secondary
reflux where a failure of normal development is
likely.
INTERNATIONAL REFLUX STUDY IN
CHILDREN
One of the most controversial topics in pediatric
urology is the treatment of vesicoureteral reflux. The International Reflux Study in Children was
organized to provide sound data on the natural
history and treatment of this condition. Although data analysis is ongoing, preliminary findings were
presented in eight separate papers, briefly reviewed
here. Van Gool from The Netherlands, in a study
based on questionnaires, demonstrated that 17% of
the children included had evidence of bladder
dys-function. These children generally had a higher
grade of reflux. The effect of this bladder
dysfunc-tion on urinary infections and reflux resolution is
uncertain on the basis of current data. Duckett of
Philadelphia analyzed the value of cystoscopy. He
noted no substantial benefit because: (1) there were large interobserver differences; (2) 37% of orifices
with no reflux were noted visually to be unfavorable in the American portion of the study; and (3) as
anticipated, high rates of abnormal orifices were
found in high grades of reflux. Hence it does not appear that cystoscopic evaluation of the orifice is reliable enough to be a predictor of the cessation of
vesicoureteral reflux. The complications of
anti-reflux surgery were reviewed in the European
sec-tion of the study by Hj#{228}lmasfrom Goteborg,
Swe-den, and in the American portion of the study by
Duckett. In the European portion of the study, 19% of the children demonstrated reflux and 5%
exhib-ited obstruction postoperatively. In contrast, in the
American portion of the study, there was no post-operative obstruction and only 9% postoperative
reflux. Obviously a comparison of the benefits of
surgery with those of medical management depends
on the success of the operative technique. With further analysis of the data it may be possible to
determine whether particular techniques are
asso-ciated with better success and fewer complications. Tamminen-M#{246}bius from Hufelandstrasse, Ger-many, reported on the disappearance rate of
vesi-coureteral reflux in those patients on medical man-agement and found that it was related directly to grading, with 65% of grades I and II disappearing
at 5 years and only 42% of grade IV. These numbers are falsely high, however, because in each instance approximately half of the cases had reappearance of reflux on later follow-up cystography. One im-portant implication is that multiple follow-up
cys-tograms are necessary to confirm the disappearance
of reflux in children on medical management. Olb-ing, also from Hufelandstrasse, reported that in
both groups the incidence of new renal scarring and
thinning was virtually identical at approximately 15%. New renal injury correlated with persistent high-grade reflux and acute pyelonephritis.
An-other interesting finding was that the majority of the scarring in the surgical group occurred early in
follow-up, whereas in the medical group it appeared
to have occurred later. Whether the new renal
injury actually occurred before treatment or
im-mediately after is unclear. Koskimies, also from
Hufelandstrasse, reported on the rate of urinary tract infection in the two groups: at 0.01 recurrence
per patient per month, it was identical in both
(although the surgical group at this point was no
longer on antibiotic prophylaxis). Interestingly, the rate of acute pyelonephritis in the surgical group
was one third of the medical group. In fact, 39 of the patients who had acute pyelonephritis during follow-up had vesicoureteral reflux, as compared with only 2 without. It does appear that surgery
significantly reduces the rate of acute
RESEARCH
Six papers were judged as the most exciting
cur-rent research. Two dealt with the effects of
extra-corporeal shock wave lithotnipsy on growing
kid-neys. In a rabbit preparation, Kaji and associates from the University of Southern California found no change in renal growth or function resulting from shock wave lithotripsy, but there was a 50% rate of hypertension, as well as renal histologic
changes proportional to the number of shocks. Neal from Tulane University, using a primate
prepara-tion, again noted no renal function changes but
markedly elevated renin in young animals undergo-ing shock wave lithotripsy. Both studies
recom-mend long-term follow-up of young children
sub-jected to this treatment. Two studies also looked at
various aspects of enterocystoplasty. Sheldon from
the University of Cincinnati demonstrated de-creased blood flow, as measured by quantitative fluorescein uptake, in colocystoplasty, primarily at antimesentenic sites and associated with distention of the cystoplasty to high intravesical pressures. This may explain the occurrence of life-threatening
spontaneous rupture after bladder augmentation. St. Clam from Wilford Hall Medical Center in San Antonio evaluated the functional aspects of
enter-ocystoplasty after delayed ligation of the pedicle.
Although gross inspection demonstrated decreased
perfusion in 50% of the animals, all survived and
only 30% demonstrated a significant decrease in bladder size or compliance. This is encouraging, as with the large number of patients undergoing en-terocystoplasty, this inadvertent complication is
likely to be encountered more often. Spencer from New York Hospital presented the results of her study of the role of androgens in testicular descent
in rats. She demonstrated that blockade of andro-gen action during gubernacular outgrowth can
pre-vent testicular descent (whereas Woiffian duct
in-hibition does not), but that blockade after
out-growth is complete does not prevent descent. Further work remains to be done in this important area. Zdenic and associates from Children’s Hospi-tal of Philadelphia won the Pediatric Urology Re-search Prize for an elegant study of developmental
aspects of urinary bladder contractile function. In particular, they found that calcium entry into blad-den smooth muscle cells via protein channels may
be altered in the neonate. This may in part account for the “spontaneous” improvement that is often seen in the asymptomatic dilated urinary tract of newborns.
The next meeting of the Section on Urology will be held October 26 to 28, 1991, in New Orleans. The Chairperson will be Edward Tank, University
of Oregon, and the Program Co-Chairs are Steven
Skoog of Walter Reed Medical Center and Gil Rushton, National Children’s Hospital, both in
Washington, DC.
CANADA TAKES A STAND ON PERTUSSIS VACCINE
ENCEPHALOPATHY
“Although there may be an increased risk of acute, severe neurologic illness (including encephalopathy) occurring within 72 hours of the administration of pertussis vaccine to previously healthy infants, the majority of such illnesses observed in the National Childhood Encephalopathy Study (NCES) in the United Kingdom were prolonged and/or complex convulsions. All such children
were normal on follow-up 12-18 months later. Reanalysis of the NCES data
has failed to confirm that there was an increased risk of permanent brain
damage following acute neurologic illness occurring within seven days of per-tussis vaccination.”
National Advisory Committee on Immunization. Canadian Immunization Guide. 3rd ed. Canada: Minister of Supply and Services; 1989.
Bowie C. Lessons from the pertussis vaccine court trial. Lancet. 1990;335:397-399.
